Mechanical properties of a medical device can be made to vary depending on the end use application for the device. For example, it is often desirable for surgical sutures to exhibit mechanical strength, such as straight tensile strength and knot tensile strength. One technique for producing surgical sutures having these desired properties is to utilize polymers having some degree of crystallinity. Specifically, the crystalline or ordered structure of the polymer imparts strength to a medical device produced therefrom, including but not limited to a surgical suture, surgical mesh, surgical staple, haemostatic clip, and the like.
In general, however, the greater the crystallinity of an absorbable polymer, the slower the rate of the absorption will be. Therefore, in those applications where an absorbable medical device is desired, there is a need to balance the level of crystallinity of the polymer against the absorbability thereof. For example, there are certain applications where there is a need for an absorbable medical device to absorb quickly, such as episiotomy and plastic surgical applications, where fast absorption of the medical device is highly desirable to improve patient comfort and to achieve aesthetic outcomes, respectively.
Several approaches to increase the absorption or hydrolysis rate of absorbable polymers are known. For example, one approach is to lower the crystallinity of the polymer to enhance the absorption or hydrolysis rate thereof. This may be done by randomizing the chemical structure of the polymer using, for example, different lactones in the copolymerization step to reduce the overall crystallinity of the polymer. However, the use of lactones to disrupt crystallinity has limited impact due to the considerably higher hydrophobicity of lactone, causing the resultant polymer and medical device to be more hydrophobic, and absorption or hydrolysis to occur more slowly. In addition, lowering the level of crystallinity of the polymer may adversely affect the physical properties of the medical device prepared therefrom.
A second approach to increase the absorption or hydrolysis rate of synthetic absorbable polymers is to add a non-absorbable hydrophilic moiety, e.g. a polyether such as polyethylene glycol (PEG), to increase the hydrophilicity of the absorbable polymer. However, such approach will result in poor mechanical properties of the medical device (e.g. tensile strength and modules) due to the general chemical structure of aliphatic polyethers, and the addition of PEG moieties will reduce the overall crystallinity of the polymers.
A third approach is to use a pre-degraded synthetic absorbable polymer. For example, an absorbable polymer may be subjected to a hydration step or gamma irradiated to initiate the hydrolysis of the absorbable polymer, thereby resulting in a pre-degraded product. However, problems arising with the use of a pre-degraded synthetic absorbable polymer include difficulty in controlling the quality and stability of the pre-degraded polymer. More specifically, it may be difficult to achieve reproducible levels of pre-degradation in the final product.
U.S. Patent Publication 2006/0051398, assigned to Ethicon, Inc., describes a copolyester comprising the reaction product of a polycondensation polyester and at least one lactone, wherein the polycondensation polyester comprises the reaction product of diglycolic acid and/or a derivative thereof and ethylene glycol. The product described in this reference is useful for adhesion prevention. Although this reference indicates that its composition is absorbable, the copolyester described in this reference is fully amorphous with relatively low molecular weight. Therefore, it is not expected that a medical device made from this copolyester will have the requisite physical properties of strength required, for example, for surgical sutures.
U.S. Patent Publication 2008/0103284, assigned to Ethicon, Inc., describes a copolyester comprising the reaction product of a polycondensation polyester and at least one lactone, wherein the polycondensation polyester comprises the reaction product of diglycolic acid and/or a derivative thereof and diethylene glycol. The copolymers described in this patent application have a very blocky glycolide structure, resulting in a relatively high crystallinity level that, in turn, slows the overall hydrolysis rate of a material. Furthermore the copolymers of this patent application exhibit a level of elasticity and strength that may not be desirable for all applications such as for surgical sutures. The application is silent about the possibility to use mixture of diols.
U.S. Pat. No. 5,644,002, also assigned to Ethicon, Inc., describes absorbable polymers and blends of polycondensation polyester and aliphatic polyesters based on lactone monomers, where the polycondensation polyester is the reaction product of diglycolic acid and an alcohol selected from selected from the group consisting of glycerol, pentaerythitol, trimethylolpropane, hydroxyl terminated poly(ethylene glycol)s, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butylene glycol, dipropylene glycol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, and 1,8-octanediol. The absorbable polymers described in this reference are branched or crosslinked fully amorphous soft materials and as such, are not expected to produce a medical device having the requisite physical properties of strength required, for example, for surgical sutures.
U.S. Pat. Nos. 4,048,256, 4,095,600 and 4,122,129, assigned to American Cyanamid Company, describe biocompatible and absorbable polycondensation polyesters, which are the polycondensation product of diglycolic acid and glycols such as ethylene glycol, diethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, and the like. Specifically, U.S. Pat. No. 4,095,600 describes a transesterification reaction product of (a) about 2 to 50% by weight of a polycondensation polyester made of diglycolic acid and an unhindered glycol and (b) polyglycolic acid (PGA) of molecular weight above 30,000 Daltons before reaction. Although it is believed that the transesterification reaction product described in this reference exhibits crystallinity, the absorbability thereof is not expected to be very good due to blocky PGA sequences and higher degree of crystal perfection of the copolymers as indicated by the high melting point of the PGA moieties. The term “BLOCKY” as used herein refers to polymeric structures containing many repeating units of the same monomer, for instance, glycolic acid, linked by covalent bonding. Low Inherent Viscosity (IV) values of the copolymers described in these references (lower than 1.0 dL/g), are not expected to yield fibers with good mechanical/tensile properties.
We now disclose a novel polymer formulation based on the reaction product of diglycolic acid and mixture of two diols, diethylene glycol (DEG) and ethylene glycol (EG). When this polycondensation product is reacted in the second, ring-opening stage with a glycolide, a copolymer with lower crystallinity is formed even in formulations containing higher glycolide content. Higher glycolide presence contributes to higher Tg, so the fibers made from this material are likely to exhibit less elasticity.
Therefore, there remains a need for a synthetic absorbable polymer that will achieve faster absorption or hydrolysis, while preserving mechanical strength that is required, for example, for surgical sutures, microspheres and nonwoven constructs.